Project Summary Abstract This project seeks to identify new molecular pathways that are involved in pain signaling. The PI has pioneered a system that uses Drosophila as a platform for discovering genes required for the function of nociceptive sensory neurons. Understanding molecular mechanisms in nociceptors is of significance because sensory drive in nociceptors contributes to the development of central sensitization and subsequent chronic pain. Furthermore, congenital pain syndromes are caused by mutations in genes that affect the function of nociceptive sensory afferents in humans. Thus, a fundamental and basic understanding of the molecular mechanisms of nociceptive neurons is important for an understanding of chronic, neuropathic, and inflammatory pain. The laboratory of the PI has conducted a genetic screen which has led to the identification of a set of genes that are of importance to the function of nociceptive neurons. During the funding period experiments will be performed that seek to elucidate the molecular, cellular and physiological mechanisms of these newly implicated molecules.